Bristol-Myers Squibb Co. said the pivotal study of lisocabtagene maraleucel (liso-cel) an investigational CD19-directed CAR T-cell therapy with a defined composition of purified CD8+ and CD4+ CAR T cells in relapsed/refractory large B-cell lymphomas (TRANSCEND NHL 001) met its primary and secondary endpoints while demonstrating durable responses.
The data were presented during an oral session at the 2019 ASH annual meeting.
“Longer-term follow-up from the TRANSCEND study shows that liso-cel resulted in a rapid, high rate of durable complete responses with low incidence of severe cytokine release syndrome and neurologic events in two and 10 percent, respectively, among patients with relapsed/refractory large B-cell lymphomas,” said Jeremy Abramson, associate professor of medicine at Harvard Medical School and director of the Lymphoma Center at Massachusetts General Hospital. “Additionally, responses with liso-cel were seen across patient groups including high-risk patients such as those with refractory disease, older patients and those with high tumor burden.”
In the study, 344 patients were leukapheresed and 269 patients received liso-cel at one of three dose levels (50 x 106 n=51; 100 x 106 n=177; and 150 x 106 n=41). There were 25 patients that received nonconforming product and there were two instances where product could not be manufactured. Patients were heavily pretreated and had aggressive disease with a median of three prior therapies including 35% with prior autologous or allogeneic hematopoietic stem cell transplant and 67% with chemotherapy-refractory disease. Bridging therapy was administered to 59% of patients.
Among patients evaluable for efficacy (n=256), the overall response rate was 73% (187/256, 95% CI: 67 – 78) with 53% of patients (136/256, 95% CI: 47 – 59) achieving a complete response. Responses were similar across all patient subgroups. The median duration of response for all patients was not reached (95% CI: 8.6 months – NR) at a median follow-up of 12 months (95% CI: 11.2 – 16.7). Median progression-free survival was 6.8 months (95% CI: 3.3 – 14.1) and median overall survival was 21.1 months (95% CI: 13.3 – NR). The median PFS and OS for patients who achieved a CR was not reached with 65.1% of patients progression free and 85.5% of patients alive at 12 months, respectively.
BMS said that based on results from TRANSCEND NHL 001 it expects to complete the submission of a Biologics License Application to FDA by the end of the year.